Structural Biology and Regulation of Protein Import into the Nucleus

doi:10.1016/j.jmb.2015.10.023

Review

. 2016 May 22;428(10 Pt A):2060-90.

doi: 10.1016/j.jmb.2015.10.023. Epub 2015 Oct 30.

Structural Biology and Regulation of Protein Import into the Nucleus

Affiliations

¹ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales Faculty of Medicine, Darlinghurst, NSW 2010, Australia.
² School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
³ Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest H-1117, Hungary; Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest H-1111, Hungary.
⁴ School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
⁵ School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
⁶ Department of Physics and Biophysics, Institute of Biosciences, Universidade Estadual Paulista, Botucatu, São Paulo 18618-000, Brazil.
⁷ School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
⁸ School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: b.kobe@uq.edu.au.

PMID: 26523678
DOI: 10.1016/j.jmb.2015.10.023

Review

Structural Biology and Regulation of Protein Import into the Nucleus

Mary Christie et al. J Mol Biol. 2016.

. 2016 May 22;428(10 Pt A):2060-90.

doi: 10.1016/j.jmb.2015.10.023. Epub 2015 Oct 30.

Authors

Affiliations

¹ The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales Faculty of Medicine, Darlinghurst, NSW 2010, Australia.
² School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
³ Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest H-1117, Hungary; Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest H-1111, Hungary.
⁴ School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
⁵ School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
⁶ Department of Physics and Biophysics, Institute of Biosciences, Universidade Estadual Paulista, Botucatu, São Paulo 18618-000, Brazil.
⁷ School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
⁸ School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: b.kobe@uq.edu.au.

PMID: 26523678
DOI: 10.1016/j.jmb.2015.10.023

Abstract

Proteins are translated in the cytoplasm, but many need to access the nucleus to perform their functions. Understanding how these nuclear proteins are transported through the nuclear envelope and how the import processes are regulated is therefore an important aspect of understanding cell function. Structural biology has played a key role in understanding the molecular events during the transport processes and their regulation, including the recognition of nuclear targeting signals by the corresponding receptors. Here, we review the structural basis of the principal nuclear import pathways and the molecular basis of their regulation. The pathways involve transport factors that are members of the β-karyopherin family, which can bind cargo directly (e.g., importin-β, transportin-1, transportin-3, importin-13) or through adaptor proteins (e.g., importin-α, snurportin-1, symportin-1), as well as unrelated transport factors such as Hikeshi, involved in the transport of heat-shock proteins, and NTF2, involved in the transport of RanGDP. Solenoid proteins feature prominently in these pathways. Nuclear transport factors recognize nuclear targeting signals on the cargo proteins, including the classical nuclear localization signals, recognized by the adaptor importin-α, and the PY nuclear localization signals, recognized by transportin-1. Post-translational modifications, particularly phosphorylation, constitute key regulatory mechanisms operating in these pathways.

Keywords: beta-karyopherin; crystal structure; importin-alpha; nuclear localization signal (NLS); nucleocytoplasmic transport.

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Structural Biology and Regulation of Protein Import into the Nucleus

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Structural Biology and Regulation of Protein Import into the Nucleus

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